Spontaneous chronic graft-versus-host disease (cGVHD) and rapidly induced cGVHD in the rat radiation chimera are clinically and histologically distinct from acute GVHD by skin histology, pattern of tissue injury and histology of lymphoid tissues. We plan to further characterize the cellular infiltrates in the target tissues and lymphoid tissues, determining the relative number and location of monocytes, T lymphocytes and Ia bearing cells. The patterns of cellular infiltrates of spontaneous chronic GVHD will be compared to acute GVHD and then to the multiple models of induced chronic GVHD in order to distinguish epiphenomena from important patterns. This characterization should provide the basis for future investigations of the pathogenesis via modification of the donor marrow and spleen cells. We plan also to continue characterizing the antigen specificity of cGVHD. The present studies have used RT-1 disparate strains (ACI and Lewis). We now have available DA rats (Rt-1a) which have only a minor antigen disparity with ACI rats. Chronic GVHD in the minor antigen mismatched chimera will be compared histologically and immunopathologically with major antigen disparate chimeras. We will further pursue the possibility of a reaction against organ specific antigens, placing renal implants of fetal skin from donor and host strain rats into chimeras with cGVHD. These studies will then complement or confirm adoptive transfer studies suggesting that cGVHD reflects a reaction against allogeneic antigens.